Division of General Internal Medicine, Los Angeles Biomedical Research Institute, Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.
J Antimicrob Chemother. 2012 Mar;67(3):715-22. doi: 10.1093/jac/dkr375. Epub 2011 Sep 20.
Host iron availability is fundamental to mucormycosis pathogenesis. The combination of liposomal amphotericin B (LAmB) and deferasirox iron chelation therapy synergistically improved survival in diabetic mice with mucormycosis. To determine the safety of combination deferasirox plus LAmB therapy for mucormycosis, a multicentred, placebo-controlled, double-blinded clinical trial was conducted.
Twenty patients with proven or probable mucormycosis were randomized to receive treatment with LAmB plus deferasirox (20 mg/kg/day for 14 days) or LAmB plus placebo (NCT00419770, clinicaltrials.gov). The primary analyses were for safety and exploratory efficacy.
Patients in the deferasirox arm (n=11) were more likely than those in the placebo arm (n=9) to have active malignancy, neutropenia and corticosteroid therapy, and were less likely to receive concurrent non-study antifungal therapy. Reported adverse events and serious adverse events were similar between the groups. However, death was more frequent in the deferasirox than in the placebo arm at 30 days (45% versus 11%, P=0.1) and 90 days (82% versus 22%, P=0.01). Global success (alive, clinically stable, radiographically improved) for the deferasirox arm versus the placebo arm at 30 and 90 days, respectively, was 18% (2/11) versus 67% (6/9) (P=0.06) and 18% (2/11) versus 56% (5/9) (P=0.2).
Patients with mucormycosis treated with deferasirox had a higher mortality rate at 90 days. Population imbalances in this small Phase II study make generalizable conclusions difficult. Nevertheless, these data do not support a role for initial, adjunctive deferasirox therapy for mucormycosis.
宿主铁的可用性对毛霉菌病发病机制至关重要。两性霉素 B 脂质体（LAmB）与地拉罗司铁螯合疗法联合使用可显著提高糖尿病毛霉菌病小鼠的生存率。为了确定联合地拉罗司和 LAmB 治疗毛霉菌病的安全性，进行了一项多中心、安慰剂对照、双盲临床试验。
20 例确诊或疑似毛霉菌病的患者被随机分为 LAmB 加地拉罗司（20mg/kg/天，连用 14 天）或 LAmB 加安慰剂治疗组（NCT00419770，clinicaltrials.gov）。主要分析为安全性和探索性疗效。
地拉罗司组（n=11）患者比安慰剂组（n=9）更有可能患有活动性恶性肿瘤、中性粒细胞减少症和皮质类固醇治疗，且更不可能接受非研究性抗真菌治疗。两组报告的不良事件和严重不良事件相似。然而，地拉罗司组的死亡率在 30 天（45%对 11%，P=0.1）和 90 天（82%对 22%，P=0.01）时高于安慰剂组。地拉罗司组和安慰剂组的 30 天和 90 天的总体成功率（存活、临床稳定、影像学改善）分别为 18%（2/11）对 67%（6/9）（P=0.06）和 18%（2/11）对 56%（5/9）（P=0.2）。
接受地拉罗司治疗的毛霉菌病患者在 90 天时死亡率更高。这项小型二期研究中存在人群失衡，使得结论难以推广。然而，这些数据不支持毛霉菌病初始辅助地拉罗司治疗的作用。
